This project is concerned with a detailed analysis of severed axons and axon sprouts in lesions of the spinal cord and optic nerve by means of electron microscopy. The zones of altered nervous tissue bordering the lesion will be mapped at various periods of time following transection of the dorsal columns. Particular attention will be devoted to the ultrastructural features of axon spouts whose intracellular relations will be analyzed in serial sections and correlated with light microscope preparations. The project is predicated on the hypothesis that functional regeneration may occur by suppressing certain aspects of the inflammatory reaction which follows the production of a lesion and that this reaction is an autoimmune response to brain antigens. Therefore, special attention will be devoted to determining the incidence and distribution of mesodermal lymphoid cells which could mediate an immune response. An attempt will be made to promote functional axon regeneration by reducing the inflammatory reaction through immunological tolerance or by the use of drugs. The efficacy of treatment will be assessed by the same mapping techniques used for normal tissue.